From the late 1970s, cryotherapy has been used in the cardiovascular system starting from, for example, 1977 when it was used to surgically treat cardiac arrhythmias. Over the ensuing years it became widely recognised that cryotherapy was particularly advantageous for working in the heart. Its safety and efficacy was unsurpassed as surgeons were able to ablate delicate cardiac structures such as the A-V node, pulmonary veins and delicate peri-nodal atrial tissue without concern for thrombosis, perforation or other adverse events.
More recently, researchers have started investigating the use of cryotherapy in the vascular system as a method to treat calcified plaque. Clinical data published by Laird et. al. “Cryoplasty for the Treatment of Femoropopliteal Arterial Disease: Extended Follow-up Results” J ENDOVASC THE 2006; 13 (Suppl II): 11-52-11-59 has shown that cryotherapy achieves good clinical results when used in highly stenosed vessels of the peripheral vasculature.
Much of this previous work has been in treating calcified plaque in patients with calcified highly stenosed vessels (>70% stenosis) as an alternative to drugs, balloon angioplasty, stents or other conventionally used therapies.
Cryotherapy typically involves applying cooling to a vessel using a catheter based balloon. A refrigerant is used to expand a balloon into contact with a target. The temperatures used in treating such calcified highly stenosed blood vessels usually range from −10° C. to −20° C. (263K to 253K) and are generally warmer than those used in the ablation field (such as those used to treat arrhythmia or for cancer tumor ablation) where refrigerant temperatures will generally be colder than −70° C. (203K). Typically, the pressure in the balloon will be above 5 atmospheres (ATM), 507 kPa, as the goal of therapies such as angioplasty is to force open critically stenosed calcified vessels.
There has also been some interest in using cryotherapy on non-critically stenosed plaque typical of so called vulnerable or unstable plaque, as exemplified by U.S. Pat. Nos. 6,673,066, 6,602,246 and 6,955,174. Vulnerable plaque, or unstable plaque, may be defined as a non-flow limiting plaque which is lipid rich with a thin cap fibroatheroma. For the purposes of the present document the terms vulnerable and unstable plaque are used interchangeably.
When such vulnerable plaque ruptures, a thrombus forms and causes a heart attack. A discussion, description and characteristics of these types of plaques is reviewed in Libby, “Atherosclerosis: The New View” Scientific American, May 2002, pg. 47. In some early work, the biological effect was poorly understood and improperly described as, for example, in U.S. Pat. No. 6,955,174 where cryotherapy treatment is described which “inhibits release of the retained fluid into the blood vessel”. It is now thought that this mechanism is incorrect and that a ruptured plaque does not release materials into the bloodstream but causes a thrombus to form at the site of rupture. This mechanism is described by Muller, “Presentation at Cardiovascular Revascularization Therapies”, March 28-31, 2005, Washington D.C., and by Fuster et al, “Atherothrombosis and High Risk Plaque”, Journal of the American College of Cardiology, 2005, Vol. 46, No. 6, pp. 937-54.
WO2012/140439 A1 discloses a known system for performing cryotherapy. A balloon catheter is positioned at a site of vulnerable plaque in a patient. A working fluid is supplied to the balloon catheter via a conduit. The working fluid may be used both as a coolant of the balloon and also to inflate the balloon. The working fluid is pumped from a reservoir and through a heat exchanger that cools the working fluid to a temperature for cryotherapy, that may be −30° C. or lower in order to achieve a sufficiently low temperature where the balloon contacts the vessel wall.
In order to perform cryotherapy, the flow rate and temperature of the working fluid supplied to the balloon need to be accurately controlled. The pressure of the fluid used to inflate the balloon of the catheter, which may be the same working fluid, also needs to be accurately controlled.
It is necessary for the working fluid to be sterile in order to limit any harm caused by an accidental leak of the working fluid from the catheter system into a patient's body. Even a small leak of a non-sterile fluid is clinically unacceptable. In order to ensure that the working fluid is sterile, it has been tried to provide inline aseptic medical filtering of the working fluid at the entry point of the catheter to a patient's body. However, when the aseptic filtering was provided in the fluid path, trials revealed the need for unexpectedly high working fluid supply pressures, resulting in the problem of the required flow rate and temperature of the working fluid being difficult to achieve.
Without the inline medical filter, the working fluid would only be sterile if all working fluid contacting parts in the pump and heat exchanger were sterilised prior to each use of the system. Clearly such sterilisation operations would be very time consuming, expensive and inconvenient. Moreover, it is not economically or practically feasible for the pump and heat exchanger to be disposable devices that are only used once since, due to the required conditions for cryotherapy, the devices need to be of a very high quality.
There is therefore a need for an improved technique for supplying a working fluid that is sterile as well as at a desired temperature and flow rate for cryotherapy.